PROJECT SUMMARY/ABSTRACT This K01 proposal will provide the applicant, Dr. Engelmann, with protected time, resources, and training to help him transition into the role of an independent researcher in the field of addiction neuroscience. Dr. Engelmann's primary research interest is to identify brain systems and deficiencies that predispose smokers to relapse. Cigarette smoking is the leading preventable cause of disease and death in the United States, and the health benefits of quitting are well known. However, most smokers who try to quit relapse. Thus, it is important to develop more effective smoking-cessation therapies. A promising approach for developing better therapies may be to target brain processes involved in relapse. Thus, Dr. Engelmann's career goal is relevant to public health and to the scope of the National Institute on Drug Abuse (NIDA), because improving smoking-cessation outcomes will reduce the burden of smoking on human health. To help Dr. Engelmann become an independent researcher, we propose a plan that will provide training and research experience under the mentorship of established, independent scientists. Training will focus on two areas: 1) functional magnetic resonance imaging (fMRI), which is a non-invasive technique for measuring brain activity, and 2) addiction psychopharmacology, which includes pharmacological treatment of nicotine dependence. With respect to each of these areas, the applicant will complete formal coursework and hands-on training and publish research findings. Research experience will include completion of a project that addresses two specific aims: 1) determine how the imminent possibility of smoking affects brain responses to cigarette-related cues and 2) determine the immediate effect of smoking on brain responses to these cues. This project is a major step forward in understanding neural processes involved in smoking relapse. Relapse often occurs in the presence of cigarette-related cues when smoking is imminently possible. However, previous brain imaging research was limited to situations where smoking was not imminently possible. The proposed project, by studying the imminent possibility and immediate effects of smoking, provides a more ecologically valid model of how these factors may precipitate smoking relapse. To achieve our specific aims, 50 smokers will complete an fMRI session in which they will smoke cigarettes inside the fMRI scanner through a special device. We will compare brain responses to cigarette cues between trials where smokers are told that they cannot smoke (i.e., smoking not possible) and trials where they are told that there is a possibility that they can smoke (i.e., smoking imminently possible). We expect brain responses in areas involved in emotional processing to be largest when smoking is imminently possible. Our findings will potentially identify new neurobiological targets for effective smoking-cessation medications. Dr. Engelmann plans to apply for future grant support to use fMRI to study the effects of existing and new medications on these targets. The training and research activities proposed in this application will help him become an independent researcher capable of obtaining this support.